Effects of Borneol on the Release of Compound Danshen Colon-Specific Osmotic Pump Capsule In Vitro and Pharmacokinetics Study in Beagle Dogs
Effects of Borneol on the Release of Compound Danshen Colon-Specific Osmotic Pump Capsule In Vitro and Pharmacokinetics Study in Beagle Dogs
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DOI：
10.1208/s12249-020-01840-8
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发表时间：
2020-11-10
影响因子：
3.3
通讯作者：
Hu, Rongfeng
中科院分区：
文献类型：
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作者：
Shao, Liangyu;Sun, Chaojie;Hu, Rongfeng
冰片可以通过打开血脑屏障和抑制 P-糖蛋白 (P-gp) 外流来增强其他几种药物的生物利用度。然而，冰片是否会影响复方丹参结肠特异性渗透泵胶囊（CDCOPC）的生物利用度及其机制尚不清楚。本研究旨在确定冰片对 CDCOPC 体外释放和体内药代动力学特征的影响。此外，通过色谱指纹图谱进一步评估了 CDCOPC 的体外释放行为。体外释放研究表明，冰片遵循零级释放，对CDCOPC中丹参和三七的体外释放几乎没有影响。而且，从指纹图谱的相似性结果可以看出，CDCOPC不同成分的体外释放几乎是同时的。与市售片剂相比，药代动力学研究表明，含冰片和不含冰片的CDCOPCs均能显着延长这些有效成分的保留时间；其平均相对生物利用度值分别增加至448.70%和350.97%。值得注意的是，冰片显着提高了 CDCOPC 中某些成分的相对生物利用度，例如 CDCOPC 中的丹酚酸 B (SAB)、丹参酮 IIA (Tan IIA)、三七皂苷 R-1 (R-1)、人参皂苷 Rg(1) (Rg(1)) 和人参皂苷 Re (Re)，而对人参皂苷 Rb-1 略有影响。 (Rb-1) 和人参皂苷 Rd (Rd)。综上所述，冰片能够提高 CDCOPC 中某些有效成分的生物利用度，这对于 CDCOPC 的设计以提高生物利用度至关重要。该研究还有助于揭示复方丹参方（CDF）的组成原理。
Borneol can enhance the bioavailability of several other drugs by opening the blood-brain barrier and inhibiting P-glycoprotein (P-gp) efflux. However, whether borneol will impact the bioavailability and the mechanism of compound Danshen colon-specific osmotic pump capsule (CDCOPC) remains unclear. This study aimed to determine the effects of borneol on the in vitro release and in vivo pharmacokinetic characteristics of CDCOPC. Besides, the in vitro release behavior of CDCOPC was further assessed by chromatographic fingerprints. The in vitro release studies showed that borneol followed the zero-order release and hardly impacted the in vitro release of Salvia miltiorrhiza and Panax notoginseng in CDCOPC. Moreover, as revealed from the similarity results of fingerprints, the in vitro release of different components of CDCOPC was almost simultaneous. Compared with the commercially available tablets, the pharmacokinetics studies suggested that both CDCOPCs containing and lacking borneol could significantly prolong the retention time of these effective components; their average relative bioavailability values increased to 448.70% and 350.97%, respectively. Notably, borneol significantly improved the relative bioavailability of some components of CDCOPC, such as salvianolic acid B (SAB), tanshinone IIA (Tan IIA), notoginsenoside R-1 (R-1), ginsenoside Rg(1) (Rg(1)), and ginsenoside Re (Re) from CDCOPC, while it slightly impacted ginsenoside Rb-1 (Rb-1) and ginsenoside Rd (Rd). Summarily, borneol is capable of improving the bioavailability of some effective components in CDCOPC, which is critical to design with CDCOPC for enhanced bioavailability. This study could also help reveal the composition principle of the compound Danshen formula (CDF).